Article date: 1988/7/7
PubMed ID: 2844552
Journal name: European journal of pharmacology (ISSN: 0014-2999)
The effects of four benzodiazepines (diazepam, clonazepam, oxazepam and clobazam) were studied on the head-twitch response induced in mice by several 5-HT receptor agonists. All the benzodiazepines tested potentiated the effects of the directly acting agonists 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine and mescaline, without themselves inducing head-twitches. In contrast, none of them potentiated head-twitches induced by the indirectly acting agonist 5-hydroxytryptophan (5-HTP; with carbidopa 25 mg/kg), and in some experiments a clear inhibition was seen. The clonazepam (10 mg/kg) potentiation of 5-MeODMT-induced head-twitches was not antagonised by flumazenil, (+)-bicuculline, or by pretreatment with p-chlorophenylalanine. Neither was it mimicked by muscimol, which inhibited head-twitches. These results indicate that the observed potentiation is not mediated by benzodiazepine receptors and that it occurs postsynaptically to the initiating 5-HT receptors. The inability of the benzodiapines to potentiate 5-HTP-induced head-twitches probably reflects a reduction in 5-HT neuronal activity mediated by benzodiazepine receptors, as co-administration of flumazenil and clonazepam potentiated the effects of 5-HTP whereas each compound alone had no effect.
Author List: Moser P C, Redfern P H
Publication Types: Journal Article
Substances mentioned in the article: Methoxydimethyltryptamines; Receptors, GABA-A; Receptors, Serotonin; Benzodiazepines; Serotonin; 5-Hydroxytryptophan;
Mesh terms: 5-Hydroxytryptophan/pharmacology; Animals; Behavior, Animal/drug effects; Benzodiazepines/pharmacology; Male; Methoxydimethyltryptamines/pharmacology; Mice; Receptors, GABA-A/drug effects; Receptors, Serotonin/drug effects; Serotonin/physiology; Synaptic Transmission/drug effects;